tbuckley/cabot-search huggingface dataset:
A glimpse into the future of hepatocellular carcinoma (HCC): Predicting the future incidence based on the current epidemiological data.
Authors: Sri Harsha Tella, Mikolaj Wieczorek, David Hodge, Amit Mahipal
Journal: Journal of Clinical Oncology (2023)

615 Background: Accounting for 90% of primary liver cancers, HCC is the fourth-most common cause of cancer-related deaths in the United States. While the vaccination against hepatitis B and awareness on hepatitis C transmission possibly decreased the incidence of HCC in Eastern World, there was an uptrend in the HCC incidence the Western World over the past few years possibly related to metabolic causes. With this changing paradigm of hepatocellular carcinoma, it is important to estimate its future burden stratified based on the age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of HCC (ICD-0-3 Site: C220 and 228; codes: 8170-8175) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future HCC incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 76029 patients with HCC were included in the final analysis. The median age was 62 (range: 20-79) years with male predominance (70%). The overall observed age-adjusted incidence of HCC between 2000-2017 was 6.22, which is predicted to increase to 9.03 by 2029 with a predominant increase in incidence rate observed in the age groups 70-79 and White males. Interestingly, we noticed a progressive decrease in incidence rate in Asian cohort (both males and females) and Black males. Incidence rates by sub-groups based on the age, sex, and race are summarized in the Table. Conclusions: We predict an overall increased incidence of hepatocellular carcinoma over the next decade in the United States, predominantly in 70-79 years age group irrespective sex and race, with an exception to Asian cohort probably representing differential risk factors. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.[Table: see text]
Cytoreductive surgery and HIPEC in colorectal cancer peritoneal metastases (CRPM): Real-world outcomes in systemic anticancer treatment–naïve patients.
Authors: Nadina Tinsley, Raghavendar Nagaraju, Sarah O'Dwyer, Michael Braun, Saifee Mullamitha, Konstantinos Kamposioras, Omer Aziz, Jorge Barriuso
Journal: Journal of Clinical Oncology (2023)

39 Background: The role of heated intraperitoneal chemotherapy (HIPEC) in colorectal cancer peritoneal metastases (CRPM) is confounded by cytoreductive surgery (CRS) or receipt of peri-operative systemic anticancer therapy (SACT). Following Prodige-7, the role of Oxaliplatin HIPEC in addition to CRS has been debated. We evaluated a patient series undergoing CRS with Oxaliplatin (368mg/m 2 for 30 mins) or Mitomycin C (MMC) (35mg/m 2 for 90 mins) HIPEC stratified by extent of CRS and SACT. Methods: Data collected retrospectively from a prospective database of CRPM patients undergoing CRS +/- HIPEC at a single UK Peritoneal Tumour Centre included sex, primary tumour detail: site, TNM stage, SACT: adjuvant, peri-operative, operation details: peritoneal cancer index (PCI), cytoreductive score (CC), HIPEC agent, molecular profile: RAS, BRAFV600E, PIK3CA, microsatellite status, date of last follow-up or recurrence/death to 1 st July 2022. Univariable and multivariable (MVA) analysis were performed for overall survival (OS) and recurrence free survival (RFS). Outcomes were compared among three patient groups: 1. all comers (all patients who underwent CRS +/- HIPEC), 2. CC0-1 (those who achieved CC0-1) and 3. SACT naïve (CC0-1 and no SACT pre-CRS, adjuvant SACT post primary resection allowed if completed &gt; 6 months). Results: From April 2005 to April 2021, 409 patients received HIPEC: 271 (66%) MMC, 138 (34%) Oxaliplatin; 395 patients (97%) had CRPM (all comers); 336 (85%) achieved CC0-1; 187 (47%) were SACT naïve. Median OS for all comer, CC0-1 and SACT naïve groups were 39, 44 and 47 months respectively. MMC vs Oxaliplatin HIPEC median OS was 44 (95% CI 38-49) vs 50 (95% 40-60) months, p=0.3 in CC0-1. Median OS in SACT naïve was 46 (95% CI 34-58) vs 60 (95% CI 38-82) months, p=0.3. Oxaliplatin HIPEC showed a trend to benefit PCI &lt;15 and SACT naïve (table). OS MVA in CC0-1 and SACT naïve showed Oxaliplatin HIPEC was comparable to MMC HR: 0.85, 95% CI (0.60-1.19) p=0.3, HR: 0.83, 95% CI (0.51-1.35) p=0.5, respectively. Oxaliplatin HIPEC had a significant benefit on local RFS in CC0-1 (MMC vs Oxaliplatin RFS 9 vs 12 months p=0.01; distant RFS 10 vs 12 months p=0.5, local and distant RFS 6 vs 8 months p=0.3). Local RFS MVA showed a HR: 0.64, 95% CI (0.41-0.99), p=0.04 for Oxaliplatin HIPEC when corrected by PCI, N stage and grade. Conclusions: The study shows a trend to better OS with Oxaliplatin HIPEC in selected patients with low volume CRPM not requiring SACT. CRS with Oxaliplatin HIPEC is beneficial in local RFS, suggesting there is a role for local control in CRPM with Oxaliplatin HIPEC. This needs to be further explored in clinical trials. [Table: see text]
Updated results of paclitaxel and cisplatin in combination with anlotinib as first-line treatment for patients with advanced ESCC: A multicenter, single-arm, open-label phase II clinical trial.
Authors: Ning Li, Tao Wu, Yong-Gui Hong, Yanzhen Guo, Yufeng Cheng, Baosheng Li, Junsheng Wang, Suxia Luo
Journal: Journal of Clinical Oncology (2023)

376 Background: Paclitaxel combined with cisplatin regimen has been the standard of care as first-line therapy in advanced ESCC for almost two decades. PD-1 blockades combined with chemotherapy as first line setting exhibited superior efficacy for patients with ESCC recently. Anlotinib was a potential second-line monotherapy for patients with ESCC in China. Therefore, this study was designed to explore the efficacy and safety of paclitaxel and cisplatin combined with anlotinib as first-line therapy in advanced ESCC. The study had been reported in 2020 ESMO (Abs 1448), 2021 ASCO-GI Symposium (Abs 181), 2021 ASCO (e16013), 2021 ESMO (Abs 1805) and 2022 ASCO-GI Symposium (Abs 315) consecutively and the update results were reported here. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and were given paclitaxel (135mg/m 2 , iv, q3w) and cisplatin (60~75mg/m 2 , iv, d1~3, q3w) plus anlotinib (10mg, po, d1~14, q3w) for 4~6 cycles as initial therapy. For those who did not have PD, maintenance treatment was adopted with anlotinib monotherapy (10mg, po, d1~14, q3w) until PD or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. The predefined sample size was 47. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and DOR. Results: From Oct 2019 to Mar 2021, a total of 47 patients were enrolled, 46 patients included in per-protocol set analysis. The best overall response indicated that there were 4 CR (8.7%), 31 PR (67.4%), 7 SD (15.2%) and 4 NE (8.7%). Consequently, ORR was 76.1% (95%CI: 61.2%-87.4%) and DCR was 91.3% (95%CI: 79.2%-97.6%). At the data cut-off date on Jan 2022, The median PFS and median OS were 8.38 months (95% CI, 6.59-10.17) and 18.53 months (95% CI, 13.11-23.95), respectively. Additionally, safety profile exhibited that the regimen was tolerable. Common grade ≥3 adverse reactions were neutropenia (17.0%), bone marrow suppression (12.8%), nausea (10.6%), and vomiting (10.6%). Conclusions: Regimen of paclitaxel and cisplatin combined with anlotinib as first-line therapy for advanced ESCC exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in phase III clinical trials. Clinical trial information: NCT04063683 .
Calculator for detection of colorectal adenomas by using artificial intelligence models in patients with chronic hepatitis C.
Authors: Maya Gogtay, Yuvaraj Singh, Anuroop Yekula, George M. Abraham
Journal: Journal of Clinical Oncology (2023)

70 Background: Hepatitis C virus (HCV) is known for its oncogenic potential, especially in hepatocellular carcinoma and non-Hodgkin lymphoma. On review, several studies have indicated that patients with chronic hepatitis C (CHC) have an increased risk of developing colorectal cancer (CRC). We developed an artificial intelligence (AI) based tool using machine learning (ML) algorithms to help stratify these patients into a higher risk of CRC/adenomas. Methods: The study was approved by the institutional review board. We developed an AI automated calculator uploaded to a graphical user interface (GUI), and we applied ML to train models to predict the probability and the number of adenomas detected on colonoscopy. Data collected were age, smoking history, significant alcohol consumption, aspirin intake, ethnicity, HCV status, gender, body mass index (BMI), and colonoscopy findings. The models can operate either in the presence or absence of the above parameters. Data sets were split into 70:30 ratios for training and internal validation. Scikit-learn StandardScaler was used to scale values of continuous variables. We used the colonoscopy findings as the gold standard and applied a deep learning architecture to train six ML models for prediction. The ML models used were Support Vector Classifier, Random Forest, Bernoulli Naïve Bayes (BNB), Gradient Boosting Classifier (GBC), Logistic Regression, and Deep Neural Networks. Additional regression models were trained and tested to predict the number of polyps. A Flask (customizable python framework) application programming interface (API) was used to deploy the trained ML model with the highest accuracy as a web application. Finally, Heroku was used for the deployment of the web-based API to https://adenomadetection.herokuapp.com. Results: Data was collected for 415 patients, of which only 206 had colonoscopy results. On internal validation with the remaining patients, BNB predicted the probability of adenoma detection with the highest accuracy of 56%, precision of 55%, recall of 55%, and F1 measure of 54%. Support Vector Regressor (SVR) predicted the number of adenomas with the least mean absolute error (MAE) of 0.905. Conclusions: Our AI-based tool shows an association between CHC and colorectal adenomas. This tool can help providers stratify patients with CHC for early referral for screening colonoscopy. Along with giving a numerical percentage, the calculator can also comment on the number of adenomatous polyps a gastroenterologist can expect while doing a colonoscopy, thus prompting a higher adenoma detection rate.
Metagenomic analysis of gut microbiota of patients with colorectal cancer at the Federal Medical Centre (FMC), Abeokuta, Ogun State, Nigeria.
Authors: Lateef Adegboyega Sulaimon, Ireoluwa Yinka Joel, Olalekan Sabur Sanusi, Quadri Arise-kola Olanipekun, Amatullah Mahe Haliru, Zainab Adedolapo Ajanaku, Aaliyah Eniola Hassan, Ikimot Fehintola Zakariyah, Faidat Bukola Ajibade, Monsurat Olajide, Modinat Olasunkanmi Lawal, Abosede Christiana Ajibare
Journal: Journal of Clinical Oncology (2023)

195 Background: It has been suggested that the intestinal microbiome plays a vital role in the development of colorectal cancer (CRC), but the changes in intestinal bacteria in healthy and CRC subjects have not yet been examined in the Nigerian population. The study sought to investigate changes in intestinal bacteria in healthy subjects and patients with CRC. Methods: Fecal samples were collected from healthy and CRC subjects at the Federal Medical Centre, Abeokuta with the study ethical approval number FMCA/47O/HREC/01/2021/23. We extracted genomic DNA with magnetic bead extraction and sequenced the whole genome using a Nanopore MinION sequencer. We performed metagenomic analysis on fecal samples from 20 healthy subjects and 20 patients with colorectal cancer (CRC) to study the bacterial community structure, relative abundance, differentially abundant bacteria, association networks, taxonomic profiling, and specialty gene expression. Results: CRC patients have significantly different bacterial community structures compared to healthy subjects. Compared to healthy subjects, CRC patients had low intestinal bacterial diversity. Only CRCs contain Gammaproteobacteria at the phylum level. Compared to CRC, Bacteroidia and Actinobacteria were significantly more abundant in healthy subjects, while Bacilli and Negativicutes were significantly less abundant. Bacteroides and Prevotella are more abundant in healthy subjects than in CRC at the genus level. There was a greater abundance of Escherichia and Pseudomonas in CRC as compared with healthy subjects. It is noteworthy that Escherichia coli, which co-occurred in both healthy and CRC subjects, was significantly elevated only in CRC, while Pseudomonas aeruginosa only occurs in CRC. Based on phylogenetic analysis, there were notable relationships between six strains of E. coli and four strains of Shigella sp. identified in CRC. There were several pathogenic-associated virulent and antimicrobial resistant genes expressed in these strains. These genes conferred resistance via antibiotic inactivation, efflux pump activity, alteration of cell wall proteins, and regulation of antibiotic permeability. Conclusions: The present study demonstrated that the taxonomic composition and functional genes of intestinal bacteria were significantly altered in CRC. Also, E. coli and P. aeruginosa are at least partially involved in the pathogenesis of CRC.
Comparison of efficacy and safety of salvage-line nivolumab monotherapy between 240 and 480 mg for advanced esophageal squamous cell carcinoma.
Authors: Yuko Murashima, Shun Yamamoto, Toshiharu Hirose, Toru Kadono, Go Ikeda, Akihiro Ohara, Mai Itoyama, Kazuki Yokoyama, Yoshitaka Honma, Koshiro Ishiyama, Junya Oguma, Hiroyuki Daiko, Ken Kato
Journal: Journal of Clinical Oncology (2023)

317 Background: Nivolumab monotherapy was established as the standard second-line treatment of advanced esophageal squamous cell carcinoma (ESCC) based on the results of the ATTRACTION-3 trial. Initially, fixed dosing of 240 mg every two weeks (240) was used according to the results of the ATTRACTION-3 trial in Feb 2020. After that, fixed dosing of 480 mg every four weeks (480) was available in clinical practice according to pharmacokinetic data on advanced melanoma in Sep 2020. However, there were little data on the efficacy and safety of these dosing for advanced ESCC patients. Methods: We retrospectively reviewed data from ESCC patients who received nivolumab monotherapy for second or later-line at our institution. We evaluated progression-free survival (PFS), objective response rate (ORR), and the incidence rate of adverse events (AEs) compared between 240 and 480. Cox proportional regression model, Fisher’s exact tests, and t-tests were used for analysis. Results: We identified 117 patients as the subject of this study. Patients characteristics in 2nd line were as followed (240 vs 480); the median age (range): 68(46-85) vs 68.5(51-84) years old, PS (0/1/2): 34/61/5% vs 54/42/4%, taxane refractory cases: 18.6 vs 53.8%. In 3rd or later line; the median age (range): 63.5(47-85) vs 58(46-80) years old, PS (0/1/2): 28/60/12% vs 14/86/0%, taxane refractory cases: 72 vs 71.4%. The ORR were 11.9 vs 24.0% in 2nd line (p=0.19), and 0 vs 14.3% in 3rd or later line (p=0.22). The median PFS was 1.7 vs 4.1 months in 2nd line (HR = 0.60; [95% CI: 0.35-1.01; p = 0.056]), and 1.4 vs 1.8 months in 3rd or later line (HR = 0.58; [95% CI: 0.23-1.46; p = 0.25]). The all-grade AEs in 58.3 vs 69.7 were observed; rash 16.7 vs 6.1%, diarrhea 9.5 vs 6.1%, adrenal insufficiency 3.6 vs 6.1%, and interstitial pneumonia 3.6 vs 15.2%. There were no treatment-related deaths. Conclusions: In this study, fixed dosing of nivolumab in 240mg and 480mg showed comparable outcomes on efficacy and safety.
Real-world effectiveness of drugs newly approved in Japan on survival in patients with advanced gastric cancer.
Authors: Toru Kadono, Satoru Iwasa, Hidekazu Hirano, Hirokazu Shoji, Natsuko Okita Okita, Atsuo Takashima, Ken Kato
Journal: Journal of Clinical Oncology (2023)

322 Background: Ramucirumab (RAM), nivolumab (NIVO), and trifluridine/tipiracil (FTD/TPI) were approved for advanced gastric cancer (AGC) between 2010 and 2020 in Japan. However, the impact of these newly approved drugs on survival in the real-world clinical setting is not clear. Methods: This retrospective study investigated the effectiveness of RAM, NIVO, and FTD/TPI in patients with performance status (PS) 0 to 2 who received doublet or triplet chemotherapy including platinum agents in first-line (1L) for advanced gastric adenocarcinoma at our hospital between 2010 and 2020. Patients were divided into two groups before or after 2017 to compare the effectiveness. Results: From a total of 825 patients, 533 were assigned to the pre-2017 group and 292 to the post-2017 group. Baseline characteristics of the pre- and post-2017 groups were, respectively, as follows: median age, 64 (range, 20-83) and 65 (25-85) years; PS 0, 206 (39%) and 89 (31%), and PS 1-2, 327 (61%) and 202 (69%); peritoneal metastasis, 334 (63%) and 189 (65%); liver metastasis, 157 (30%) and 68 (23%); and HER2 positive, 82 (15%) and 57 (20%). There was no difference in the proportion of fluoropyrimidine and platinum agents between the two groups. For the pre- and post-2017 groups, 1L chemotherapy comprised fluoropyrimidine plus platinum agents (FP) for 71% and 68% of patients, FP plus taxanes for 15% and 1%, FP plus trastuzumab for 11% and 15%, and FP plus immune checkpoint inhibitors (ICIs) for 1% and 10%, respectively. Taxanes and irinotecan were used significantly more often in any treatment line in the pre-2017 group (taxanes, 74% vs. 64%, p&lt;0.01; irinotecan, 32% vs. 7%, p&lt;0.01), whereas RAM, ICIs, and FTD/TPI were used significantly more often in any line in the post-2017 group (RAM, 50% vs. 17%, p&lt;0.01; ICIs, 48% vs. 9%, p&lt;0.01; FTD/TPI, 6% vs. 0%, p&lt;0.01). Overall survival was significantly longer in the post-2017 group than in the pre-2017 group (median, 16.9 months vs. 13.8 months, HR 0.74, p&lt;0.01). Progression-free survival did not differ between the pre- and post-2017 groups in relation to 1L (median, 6.0 vs. 5.9 months, p=0.74); second-line treatment (median, 3.0 months [95%CI, 2.6-3.3] vs. 3.1 months [95%CI, 2.3-3.6]; HR 0.96 [95%CI, 0.82-1.14], p=0.57); third-line treatment (median, 2.1 months [95%CI, 1.8-2.5] vs. 1.8 months [95%CI, 1.4-2.1]; HR 1.03 [95%CI, 0.82-1.29], p=0.80); or fourth-line treatment (median, 1.9 months [95%CI, 1.7-2.5] vs. 1.8 months [95%CI, 1.5-2.8]; HR 0.85 [95%CI, 0.57-1.25], p=0.39). Rates of second-, third-, and fourth-line treatment in the pre- and post-2017 groups were 83% and 79% (p=0.23), 45% and 56% (p&lt;0.01), 16% and 22% (p=0.07), respectively. Conclusions: Newly approved drugs in salvage-line treatment of AGC may have contributed to prolonged survival.
Responses to first-line systemic therapies in patients with hepatocellular carcinoma with TERT promoter mutations.
Authors: Jeremy Chang, Kathryn J Fowler, Pablo Tamayo, Adam Burgoyne
Journal: Journal of Clinical Oncology (2023)

589 Background: The treatment landscape of advanced hepatocellular carcinoma (HCC) has made significant advances with the use of oral multikinase inhibitors and immunotherapy-containing regimens. However, there is minimal data with regards to which biomarkers may predict treatment responses in this population. The increased use of next-generation sequencing (NGS) has identified the most frequent mutations in HCC, including TERT promoter mutations which are found in up to 65% of patients. With the high frequency of these mutations, additional studies are needed to investigate their associations with treatment outcomes. Methods: Our team performed a retrospective study to determine the association between TERT promoter mutations in HCC and responses to first-line systemic therapies. All patients in this study underwent NGS testing on tumor tissue or peripheral blood samples. Responses to treatment were determined by imaging at least 6 weeks after the start of systemic therapy. Results: There were 128 HCC patients included in this study with TERT promoter mutations found in 72 patients (56.3%). All patients received first-line therapy with either an immunotherapy-based regimen or oral multikinase inhibitor monotherapy (lenvatinib or sorafenib). When looking at responses to all first-line therapies, patients with TERT promoter mutations were found to have significantly higher rates of disease progression (PD) compared to those without TERT promoter mutations (34.7% vs 17.9%, p = 0.04). In addition, when stratifying responses by type of systemic therapy, the TERT promoter-mutated population had notably higher rates of PD with immunotherapy regimens compared to patients without TERT mutations (34.6% vs 10.8%, p = 0.01). In contrast, there was no significant difference in rates of PD with oral multikinase inhibitor monotherapy between TERT mutated and TERT non-mutated individuals (35% vs 31.6%, p = 1). See table for further details. Conclusions: In this study, HCC patients with TERT promoter mutations were found to have significantly higher rates of PD to first-line therapies and, specifically, immunotherapy-containing regimens. Given the prevalence of these mutations in the HCC population, further investigation is needed to clarify this association and its impact on patient survival.[Table: see text]